RRC ID 31341
Author Liu T, Yamaguchi Y, Shirasaki Y, Shikada K, Yamagishi M, Hoshino K, Kaisho T, Takemoto K, Suzuki T, Kuranaga E, Ohara O, Miura M.
Title Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response.
Journal Cell Rep
Abstract Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1β (IL-1β). Although the dynamics of caspase-1 activation, IL-1β secretion, and cell death have been examined with bulk assays in population-level studies, they remain poorly understood at the single-cell level. In this study, we conducted single-cell imaging using a genetic fluorescence resonance energy transfer sensor that detects caspase-1 activation. We determined that caspase-1 exhibits all-or-none (digital) activation at the single-cell level, with similar activation kinetics irrespective of the type of inflammasome or the intensity of the stimulus. Real-time concurrent detection of caspase-1 activation and IL-1β release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1β in a digital manner, which identified these macrophages as the main source of IL-1β within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases.
Volume 8(4)
Pages 974-82
Published 2014-8-21
DOI 10.1016/j.celrep.2014.07.012
PII S2211-1247(14)00579-8
PMID 25127135
MeSH Animals Caspase 1 / physiology* Cells, Cultured Enzyme Activation Humans Inflammasomes / metabolism* Interleukin-1beta / physiology Kinetics Lipopolysaccharides / pharmacology Macrophages, Peritoneal / enzymology Macrophages, Peritoneal / immunology Mice, Transgenic Signal Transduction Single-Cell Analysis
IF 8.109
Times Cited 81
WOS Category CELL BIOLOGY
Altmetric score
オルトメトリクス指標項目
The most frequently cited source X(Twitter)
Total number of mentions 12
Altmetric score changes over past 6months 0.0
Resource
Mice RBRC01828